Dissertation Defence: Darius Gaymon

Candidate Name: Darius Gaymon

Major: Tumor Biology

Advisor: Michael Johnson, Ph.D.

Title: ROS-Mediated Matriptase Activation Contributes to ER-Negative Proliferation and Migration and Directs NAC Treatment in Several Carcinomas

Matriptase is a type-II serine protease that is widely expressed in epithelial tissues and is known to have a role in normal epithelial cell integrity. Matriptase expression and activation are normally tightly regulated by its cognate inhibitor, Hepatocytpe Growth Factor Activator Inhibitor-1, HAI-1, but is often deranged in many cancers and correlates with poor patient prognoses. Matriptase is known to act as an oncogene and has been shown to activate tumor promoting substrates such as uPA, PAR2 and pro-HGF. Matriptase activation correlates universally with inflammatory conditions such as low pH and has been shown to occur as a result of stimulation with compounds such as sphingosine 1-phosphate (S-1P) in A1N4 breast cancer cells. In this thesis, we have shown that EGFR-directed matriptase activation contributes to proliferation and migration in ER-negative breast cancer. We have also shown that matriptase activation returns with Lapatinib resistance in HER2-amplified breast cancer. Finally, we have demonstrated that ROS is central to the mechanism of matriptase activation and have used matriptase activation to direct N-acetyl cysteine (NAC) treatment in several carcinomas. This work is promising for the future clinical use of matriptase as well as the study of matriptase in other ROS-dependent malignancies.

Tuesday, March 12 at 12:00pm to 2:00pm


New Research Building, Auditorium
3800 Reservoir Road, N.W., Washington

Event Type

Academic Events, Dissertation Defense

Departments

Biomedical Graduate Education, Tumor Biology Training Program, Graduate School of Arts and Sciences

Cost

Free

Open to the public and the press?

Yes

Event Contact Name

Jadyn Stewart

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